B. Field of the Invention
The invention relates to methods of coating particles, and the particles produced thereby. More specifically, the invention relates to drug particles or drug delivery particles coated with a material, which may be biodegradable or biocompatible, such as a polymer. The coating may impart a number of characteristics to the particle including altering its surface properties, its rate of dissolution, or its rate of diffusion and/or release of an active component. More particularly, the invention provides methods for preparing particulate compositions that are coated with ultrafine layers of coating materials, preferably organic polymeric coating materials, applied through a non-aqueous, non-solvent technique. A particularly preferred process is a vapor deposition process such as pulsed laser ablation. Among the many advantages of the disclosed methods are control of both the thickness and uniformity of the coating on the surfaces of the selected particulate drug.
C. Description of Related Art
Pharmaceutical formulations that provide for delivery of a drug over an extended period of time have revolutionized the pharmaceutical industry. Whether the delivery is sustained, modified, controlled, extended, or delayed, the concept is generally the same—provide in a single dose what previously required multiple doses. (“Sustained release” will be used herein to describe this generic class of release mechanisms.) The desire is to provide an effective concentration of the drug for an appropriate length of time.
There are several advantages to such formulations. For example, having a lower concentration of the drug in the body for a longer period of time lowers the incidence of toxicity for drugs with a narrow therapeutic window, and often improves the overall effect. Also, patient compliance is improved when the dosing regimen is decreased; a patient is far more likely to take a single daily dose, than to take two, three, or even four doses daily. This is true for drugs delivered orally, as well as those which are injected, inhaled, or delivered by transdermal or transmucosal diffusion.
Traditionally, sustained release has been achieved by placing a coating material over the drug particles or granules. Thus, tablets, capsules, caplets, pills, and other formulations with coated granules have been provided. Depending on the desired drug release properties, a drug core may be coated with a single layer of coating, or alternating coatings may be provided, or the drug may actually be interdispersed within a coating material. The possibilities are numerous, and the particulars of the formulation are chosen based on the desired drug release properties. A summary of such formulations is provided in Modern Pharmaceutics, Second Edition, edited by Gilbert S. Banker and Christopher T Rhodes, the entire contents of which is hereby incorporated by reference.
Oral and other sustained release deliver; systems have largely been based on solvent-based particulate or matrix-type systems. These systems utilize spray-coating or mechanical mixing of a core drug particle and/or excipient granule with a polymer, e.g., a cellulose, polyacrylate, degradable polyester, etc., to control the rate of release of the active drug substance. In addition, traditional matrix systems may contain a gel-forming excipient, e.g., polyvinyl alcohol (PVA), polyethylene oxide (or polyethylene glycol, PEG), celluloses, etc., that form a gel layer after delivery that releases the drug over time by diffusion of the drug through the matrix. A limitation of these systems is that multi-stage scale-up from the laboratory to commercial-scale production of formulations can be lengthy and difficult, often requiring specialized equipment and expensive solvents. Additionally, known systems produce formulations that have a relatively high concentration of polymer, thick coatings, and tend not to be reproducibly manufactured with identical release profiles.
Therefore, what is needed are improved methods for preparing coated drug particles that do not suffer these limitations, and that are useful in preparing pharmaceutical formulations with superior drug delivery and efficacy properties.